Rats represent the most commonly used physiologically and pharmacological experimental model for studying human disease. The ability to genetically modify rats through methods of gene transfer in fertilized rat embryos or by gene targeting in embryonic stem (ES) cells has significantly increased the capabilities of rats in biomedical and pharmaceutical research. Until now, the production of targeted gene- modifications in rats requires the surgical transfer of embryos. This surgery is cost and labor intensive since it requires anesthesia (with potential complications), post-operative care of female rats (which may include the use of analgesics), as well as technical expertise on the part of the person carrying out the surgery. At the same time, there is a strong desire in the animal research community to reduce the morbidity, stress, and pain of animals used for research purposes. To overcome these problems we propose to develop a Non-Surgical Embryo Transfer (NSET) device that can be used for the non-surgical transfer of embryos into female rats. We have previously developed a device for use in mice that is rapid, does not require surgery (including the associated anesthesia and post-operative care), requires little expertise, and preliminarily is as efficacious as standard surgical embryo transfer in the production of transgenic mice. Although the rat reproductive tract anatomy is significantly different than that of mice, we believe we can successfully develop a rat NSET device prototype. The aims of this proposal are to design a rat NSET prototype, manufacture the prototype device, and demonstrate device efficacy for non-surgical transfer of embryos. Success in these aims will provide the foundation to seek a Phase II award and for the commercialization of the NSET device for academic and bio/pharma rat research facilities. PUBLIC HEALTH RELEVANCE: The development of a device for the non-surgical transfer of embryos into recipient female rats represents a substantial advance over existing methods for generating gene-modified rats by eliminating surgery, anesthesia, and post-operative care. The goal of this proposal is to develop, manufacture, and determine the efficacy of a non- surgical embryo transfer prototype device for the transfer of rat embryos.